OBJECTIVE: The aim of the present study was to compare between two antioxidant treatments in prevention of fenitrothion induced toxicity on rat parotid salivary gland. DESIGN: Forty adult male Wistar rats with an average weight of 120-150 g were randomised into 4 groups, control (group I), fenitrothion administration (group II), fenitrothion administration 1h after green tea extract or nigella sativaoil extract administration (groups III and IV respectively). The rats were then sacrificed after 28 days. The submandibular salivary glands were examined histologically, immunohistochemically and ultrastructurally. RESULTS: Histopathologically the fenitrothion group showed sign of acini degeneration represented by loss of normal architecture (amalgamation). The nuclei of the acinar cells revealed different sizes and shape (polymorphism). The acini relatively preserved their shape in both prophylactic groups (III and IV). Histomorphometric analysis showed significant increase in the optical density of caspase-3 cleaved activity in all experimental groups (p=0.0001). A significant difference was observed between both prophylactic experimental groups III and IV (p=0.0039). Ultrastructurally, the nuclei of serous acini in group II appeared pyknotic with segregation of chromatin. Condensation of the chromatin at the periphery of the nucleus was observed in the nuclei of group III, Clumping of the chromatin with darkly stained pyknotic nucleus was detected in group IV. CONCLUSIONS: In a rat model the administration of natural antioxidants could be of beneficial effect on prevention of cytotoxicity induced by organophosphorous compounds. However, green tea showed more promising results than that of Nigella sativa.